Browsing by Subject "Taperin"

Now showing 1 - 2 of 2
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    GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing
    (Elsevier, 2018-10-30) Liu, Chang; Luo, Na; Tung, Chun-Yu; Perrin, Benjamin J.; Zhao, Bo; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Mutations in human GRXCR2, which encodes a protein of undetermined function, cause hearing loss by unknown mechanisms. We found that mouse GRXCR2 localizes to the base of the stereocilia, which are actin-based mechanosensing organelles in cochlear hair cells that convert sound-induced vibrations into electrical signals. The stereocilia base also contains taperin, another protein of unknown function required for human hearing. We show that taperin and GRXCR2 form a complex and that taperin is diffused throughout the stereocilia length in Grxcr2-deficient hair cells. Stereocilia lacking GRXCR2 are longer than normal and disorganized due to the mislocalization of taperin, which could modulate the actin cytoskeleton in stereocilia. Remarkably, reducing taperin expression levels could rescue the morphological defects of stereocilia and restore the hearing of Grxcr2-deficient mice. Thus, our findings suggest that GRXCR2 is critical for the morphogenesis of stereocilia and auditory perception by restricting taperin to the stereocilia base.
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    Reducing Taperin Expression Restores Hearing in Grxcr2 Mutant Mice
    (Elsevier, 2022) Liu, Chang; Luo, Na; Zhao, Bo; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Recessive mutations in GRXCR2 cause deafness in both humans and mice. In Grxcr2 null hair cells, the sensory receptors for sound in the inner ear, stereocilia are disorganized. Reducing the expression of taperin, a protein that interacts with GRXCR2 at the base of stereocilia, corrects the morphological defects of stereocilia and restores hearing in Grxcr2 null mice. To further validate this finding, this study generated two novel taperin mutant mouse lines that exhibit progressive hearing loss. Then Grxcr2 null mice were crossed with one of these taperin mutant mice. The following morphological analysis revealed that reducing taperin expression indeed corrected stereocilia morphological abnormalities in Grxcr2 null mice. Functional analysis further confirmed that reducing taperin expression partially restored hearing in Grxcr2 null mice.